A large meta-analysis identifies genes associated with anterior uveitis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 11 2023
11 11 2023
Historique:
received:
07
04
2023
accepted:
30
10
2023
medline:
13
11
2023
pubmed:
11
11
2023
entrez:
10
11
2023
Statut:
epublish
Résumé
Anterior Uveitis (AU) is the inflammation of the anterior part of the eye, the iris and ciliary body and is strongly associated with HLA-B*27. We report AU exome sequencing results from eight independent cohorts consisting of 3,850 cases and 916,549 controls. We identify common genome-wide significant loci in HLA-B (OR = 3.37, p = 1.03e-196) and ERAP1 (OR = 0.86, p = 1.1e-08), and find IPMK (OR = 9.4, p = 4.42e-09) and IDO2 (OR = 3.61, p = 6.16e-08) as genome-wide significant genes based on the burden of rare coding variants. Dividing the cohort into HLA-B*27 positive and negative individuals, we find ERAP1 haplotype is strongly protective only for B*27-positive AU (OR = 0.73, p = 5.2e-10). Investigation of B*27-negative AU identifies a common signal near HLA-DPB1 (rs3117230, OR = 1.26, p = 2.7e-08), risk genes IPMK and IDO2, and several additional candidate risk genes, including ADGFR5, STXBP2, and ACHE. Taken together, we decipher the genetics underlying B*27-positive and -negative AU and identify rare and common genetic signals for both subtypes of disease.
Identifiants
pubmed: 37949852
doi: 10.1038/s41467-023-43036-1
pii: 10.1038/s41467-023-43036-1
pmc: PMC10638276
doi:
Substances chimiques
HLA-B Antigens
0
ERAP1 protein, human
EC 3.4.11.-
Aminopeptidases
EC 3.4.11.-
Minor Histocompatibility Antigens
0
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7300Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001878
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001881
Pays : United States
Investigateurs
Aaron Zhang
(A)
Adam J Mansfield
(AJ)
Adam Locke
(A)
Aditeya Pandey
(A)
Adrian Campos
(A)
Arkopravo Ghosh
(A)
Alexander Gorovits
(A)
Alexander Lopez
(A)
Alicia Hawes
(A)
Alison Fenney
(A)
Amelia Averitt
(A)
Amit Joshi
(A)
Amy Damask
(A)
Andrew Bunyea
(A)
Andrey Ziyatdinov
(A)
Anita Pandit
(A)
Ann Perez-Beals
(A)
Anna Alkelai
(A)
Anthony Marcketta
(A)
Antoine Baldassari
(A)
Ariane Ayer
(A)
Arthur Gilly
(A)
Ayesha Rasool
(A)
Aysegul Guvenek
(A)
Benjamin Geraghty
(B)
Benjamin Sultan
(B)
William Palmer
(W)
Bin Ye
(B)
Blair Zhang
(B)
Boris Boutkov
(B)
Brian Hobbs
(B)
Caitlin Forsythe
(C)
Carlo Sidore
(C)
Charles Paulding
(C)
Chenggu Wang
(C)
Christina Beechert
(C)
Christopher Gillies
(C)
Chuanyi Zhang
(C)
Cristen J Willer
(CJ)
Dadong Li
(D)
Deepika Sharma
(D)
Eli Stahl
(E)
Eliot Austin
(E)
Eric Jorgenson
(E)
Erin D Brian
(ED)
Ernst Mayerhofer
(E)
Evan Edelstein
(E)
Evan K Maxwell
(EK)
Gannie Tzoneva
(G)
George Hindy
(G)
George Mitra
(G)
Gina Solari
(G)
Gisu Eom
(G)
Hang Du
(H)
Hossein Khiabanian
(H)
Jack Kosmicki
(J)
Jacqueline Otto
(J)
Jaimee Hernandez
(J)
Janice Clauer
(J)
Jason Mighty
(J)
Jeffrey C Staples
(JC)
Jennifer Rico-Varela
(J)
Jessie Brown
(J)
Jing He
(J)
Jingning Zhang
(J)
Joana Revez
(J)
Jody Hankins
(J)
Joelle Mbatchou
(J)
Johannie Rivera-Picart
(J)
John Silver
(J)
Jonas Bovijn
(J)
Jonathan Marchini
(J)
Jonathan Ross
(J)
Jose Bras
(J)
Joseph Herman
(J)
Joshua Backman
(J)
Ju Guan
(J)
Juan Rodriguez-Flores
(J)
Justin Mower
(J)
Karl Landheer
(K)
Kathie Sun
(K)
Kathy Burch
(K)
Kayode Sosina
(K)
Kia Manoochehri
(K)
Kimberly Skead
(K)
Krishna Pawan Punuru
(KP)
Kristy Guevara
(K)
Kuan-Han Wu
(KH)
Kyoko Watanabe
(K)
Lance Zhang
(L)
Laura M Cremona
(LM)
Lauren Gurski
(L)
Lei Chen
(L)
Liron Ganel
(L)
Luanluan Sun
(L)
Lukas Habegger
(L)
Manasi Pradhan
(M)
Manav Kapoor
(M)
Manuel Allen Revez Ferreira
(MAR)
Marcus B Jones
(MB)
Maria Sotiropoulos Padilla
(MS)
Maria Cristina Suciu
(MC)
Maya Ghoussaini
(M)
Mary Haas
(M)
Michael Lattari
(M)
Michael Kessler
(M)
Michelle G LeBlanc
(MG)
Michelle Pagan
(M)
Mira Tang
(M)
Moeen Riaz
(M)
Mona Nafde
(M)
Mudasar Sarwar
(M)
Nadia Rana
(N)
Nan Lin
(N)
Niek Verweij
(N)
Nilanjana Banerjee
(N)
Nirupama Nishtala
(N)
Olga Krasheninina
(O)
Oliver Delaneau
(O)
Olukayode Sosina
(O)
Parsa Akbari
(P)
Peter Dornbos
(P)
Peter VandeHaar
(P)
Prathyusha Challa
(P)
Priyanka Nakka
(P)
Randi Schwartz
(R)
Raymond Reynoso
(R)
Razvan Panea
(R)
Ricardo Schiavo
(R)
Rita Guerreiro
(R)
Rouel Lanche
(R)
Sailaja Vedantam
(S)
Salvador Romero Martinez
(SR)
Sam Choi
(S)
Samantha Zarate
(S)
Sameer Malhotra
(S)
Samuel Hart
(S)
Sanjay Sreeram
(S)
Sarah E Wolf
(SE)
Sarah Graham
(S)
Scott Vrieze
(S)
Sean O'Keeffe
(S)
Sean Yu
(S)
Sheila Gaynor
(S)
Silvia Alvarez
(S)
Suganthi Balasubramanian
(S)
Sujit Gokhale
(S)
Sunilbe Siceron
(S)
Suying Bao
(S)
Tanima De
(T)
Timothy Thornton
(T)
Tommy Polanco
(T)
Tyler Joseph
(T)
Valentina Zavala
(V)
Vijay Kumar
(V)
Vrushali Mahajan
(V)
William J Salerno
(WJ)
Xiaodong Bai
(X)
Yuxin Zou
(Y)
Zhenhua Gu
(Z)
Adolfo Ferrando
(A)
Alan Shuldiner
(A)
Andrew Deubler
(A)
Aris Economides
(A)
Gonçalo Rocha Abecasis
(GR)
Jeffrey G Reid
(JG)
John D Overton
(JD)
Katherine Siminovitch
(K)
Luca A Lotta
(LA)
Lyndon J Mitnaul
(LJ)
Michael Cantor
(M)
Informations de copyright
© 2023. The Author(s).
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